Effects of Bitter Substances on Energy Intake and Blood Glucose, and Associated Gastrointestinal Functions, in Healthy Humans

Abstract

The studies in this thesis investigated whether specific bitter compounds, administered intraduodenally or intragastrically, reduce postprandial blood glucose and/or energy intake in healthy humans, by modulating GI functions, e.g. gut hormones, gut motility and gastric emptying. The key findings of the studies are: 1. Slow intraduodenal infusion of quinine, providing doses of 37.5, 75 and 225 mg, over 60 min, did not affect antropyloroduodenal motility, plasma CCK or energy intake, possibly because the delivery rate was insufficient to activate duodenal bitter taste receptors (Chapter 2). 2. Intragastric bolus administration of quinine, at doses of 275 and 600 mg, slightly stimulated insulin, and, in response to a mixed-nutrient drink, consumed 30 min later, lowered plasma glucose, associated with markedly increased insulin and modest increases in glucagon and GLP-1, but did not slow gastric emptying, suggesting that, in this study paradigm, postprandial blood glucose lowering was primarily due to insulin (Chapter 3). 3. Both intragastric and intraduodenal administration of quinine (600 mg), administered 60 min or 30 min, respectively, before consumption of a mixed-nutrient drink, markedly stimulated C-peptide and reduced plasma glucose, both alone and following the drink, and slowed gastric emptying, with no difference between the routes of administration. The data suggest that, intragastric quinine, when allowed sufficient time to interact with intestinal bitter-taste receptors, reduces blood glucose, by stimulating insulin and slowing gastric emptying, comparably with intraduodenal quinine (Chapter 4). 4. Intraduodenal administration of a bitter extract from hops flowers, Humulus lupulus L., only had a modest, and transient, effect to stimulate pyloric pressure, and a delayed effect to stimulate PYY (~ 60 min post-administration), but did not affect antral or duodenal pressures, CCK or energy intake. While the intragastric study part needs to be completed, it appears that intragastric delivery of hops extract may have a more potent, and persistent, effect to stimulate pyloric pressure than intraduodenal delivery. While these findings may suggest that bitter hops extract, in contrast to quinine, may have a greater effect on gastric bitter receptors, the study will need to be completed to draw more definitive conclusions (Chapter 5). In conclusion, the research presented in this thesis has established that bitter compounds, including quinine and hops extract, vary in their potency, and effects, on GI functions, i.e. secretion of gut hormones, modulation of gut motility and/or gastric emptying, that are associated with regulation of energy intake and/or blood glucose. Quinine had potent glucose-lowering effects, mediated by both gastric emptying and stimulation of glucoregulatory hormones, including insulin, while the role of GLP-1 is less clear. In contrast, the effects of hops extract remain less clear. Further research is warranted to investigate the suitability of these, and other, bitter compounds as novel and effective management or treatment strategies for type 2 diabetes and/or obesity.